tbuckley/cabot-search huggingface dataset:
Molecular Engineering Design of Enhanced Donor–Acceptor Therapeutic Reagent for Efficient Image‐Guided Photodynamic Therapy
Authors: Tingting Zhao, Yanli Xu, Rui Liu, Xiaofei Shang, Ciyuan Huang, Wuqi Dong, Min Long, Bingsuo Zou, Xianwen Wang, Gang Li, Yuxian Shen, Tao Liu, Bo Tang
Journal: Advanced Healthcare Materials (2023)

The greatest barrier to the further development and clinical application of tumor image-guided photodynamic therapy (PDT), is the inconsistency between the fluorescence intensity and singlet oxygen generation yield of the photosensitizer under light excitation. Herein, a novel donor-acceptor (D-A) system is designed from the point of molecular selection by wrapping a classical porphyrin molecule (5,10,15,20-tetraphenylphorphyrin, H2 TPP) as an acceptor into conjugated polymer (Poly[N,N'-bis(4-butylpheny)-N,N'-bis(phenyl)benzidine], ADS254BE) as a donor through fluorescence resonance energy transfer (FRET) mechanism, which exhibits bright red emission centered at 650 nm (quantum yield, 0.12), relatively large Stoke shift of 276 nm, enhanced singlet oxygen generation rate of 0.73, and excellent photostability. The investigations on distribution and killing effect of nanomaterials in cancer cells reveal that ADS254BE/H2 TPP NPs can accumulate in the cytoplasm for imaging while simultaneously producing a large amount of singlet oxygen to remarkably kill cancer cells, which can be used for real-time image-guided PDT. In the xenograft tumor model, real-time imaging and long-term tracing in tumor tissue with ADS254BE/H2 TPP NPs disclose that the growth of lung cancer in mice can be effectively inhibited during in situ imaging. From the standpoint of molecular engineering design, this work provides a feasible strategy for novel D-A systems to improve the development of image-guided PDT.
Programmable Peptides Activated Macropinocytosis for Direct Cytosolic Delivery
Authors: Yan‐Lei Fan, Ni‐Yuan Zhang, Da‐Yong Hou, Yi Hao, Rui Zheng, Jia Yang, Zhi Fan, Hong‐Wei An, Hao Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Bioactive macromolecules show great promise for the treatment of various diseases. However, the cytosolic delivery of peptide‐based drugs remains a challenging task owing to the existence of multiple intracellular barriers and ineffective endosomal escape. To address these issues, herein, programmable self‐assembling peptide vectors are reported to amplify cargo internalization into the cytoplasm through receptor‐activated macropinocytosis. Programmable self‐assembling peptide vector‐active human epidermal growth factor receptor‐2 (HER2) signaling induces the receptor‐activated macropinocytosis pathway, achieving efficient uptake in tumor cells. Shrinking macropinosomes accelerate the process of assembly dynamics and form nanostructures in the cytoplasm to increase peptide‐based cargo accumulation and retention. Inductively coupled plasma mass (ICP‐MS) spectrometry quantitative analysis indicates that the Gd delivery efficiency in tumor tissue through the macropinocytosis pathway is improved 2.5‐fold compared with that through the use of active targeting molecular delivery. Finally, compared with nanoparticles and active targeting delivery, the delivery of bioactive peptide drugs through the self‐assembly of peptide vectors maintains high drug activity (the IC 50 decreased twofold) in the cytoplasm and achieves effective inhibition of tumor cell growth. Programmable self‐assembling peptide vectors represent a promising platform for the intracellular delivery of diverse bioactive drugs, including molecular drugs, peptides, and biologics.
Composite Flexible Sensor Based on Bionic Microstructure to Simultaneously Monitor Pressure and Strain
Authors: Meng Wang, Zhaohua Lin, Suqian Ma, Yingqing Yu, Boya Chen, Yunhong Liang, Lei Ren
Journal: Advanced Healthcare Materials (2023)

To achieve the human sense of touch, a strain sensor needs to be coupled with a pressure sensor to identify the compliance of the contacted material. However, monitoring the pressure-strain signals simultaneously and ensuring no coupling effect between the two signals is the technical bottleneck for the flexible tactile sensor to. Herein, a composite flexible sensor based on microstructures of lotus leaf is designed and manufactured, which integrates the capacitive pressure sensor and the resistance strain sensor into one pixel to realize the simultaneous detection of pressure and strain. The electrode layer of the capacitance sensor also plays the role of the resistance strain sensor, which greatly simplifies the structure of the composite flexible sensor and obtains the compact size to integrate more easily. The device can simultaneously detect pressure and deformation, and more importantly, there is no coupling effect between the two kinds of signals. Here, the sensor has high pressure sensitivity (0.784 kPa-1 when pressure less than 100 kPa), high strain sensitivity (gauge factor = 4.03 for strain 0-40%), and can identify materials with different compliance, which indicates the tactile ability as the human skin performs.
Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome
Authors: Lucia Salz, Alexander Seitz, Daniel Schäfer, Julia Franzen, Tatjana Holzer, Carlos A. Garcia-Prieto, Iris Bürger, Olaf Hardt, Manel Esteller, Wolfgang Wagner
Journal: Leukemia (2023)

Abstract Chimeric antigen receptor (CAR) T cells provide new perspectives for treatment of hematological malignancies. Manufacturing of these cellular products includes culture expansion procedures, which may affect cellular integrity and therapeutic outcome. In this study, we investigated culture-associated epigenetic changes in CAR T cells and found continuous gain of DNAm, particularly within genes that are relevant for T cell function. Hypermethylation in many genes, such as TCF7 , RUNX1 , and TOX , was reflected by transcriptional downregulation. 332 CG dinucleotides (CpGs) showed an almost linear gain in methylation with cell culture time, albeit neighboring CpGs were not coherently regulated on the same DNA strands. An epigenetic signature based on 14 of these culture-associated CpGs predicted cell culture time across various culture conditions. Notably, even in CAR T cell products of similar culture time higher DNAm levels at these CpGs were associated with significantly reduced long-term survival post transfusion. Our data demonstrate that cell culture expansion of CAR T cells evokes DNA hypermethylation at specific sites in the genome and the signature may also reflect loss of potential in CAR T cell products. Hence, reduced cultivation periods are beneficial to avoid dysfunctional methylation programs that seem to be associated with worse therapeutic outcome.
Novel mechanisms of salt-sensitive hypertension
Authors: Liffert Vogt, Francine Z. Marques, Toshiro Fujita, Ewout J. Hoorn, A.H. Jan Danser
Journal: Kidney International (2023)

A high dietary sodium-consumption level is considered the most important lifestyle factor that can be modified to help prevent an increase in blood pressure and the development of hypertension. Despite numerous studies over the past decades, the pathophysiology explaining why some people show a salt-sensitive blood pressure response and others do not is incompletely understood. Here, a brief overview of the latest mechanistic insights is provided, focusing on the mononuclear phagocytic system and inflammation, the gut-kidney axis, and epigenetics. The article also discusses the effects of 3 types of novel drugs on salt-sensitive hypertension-sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and aldosterone synthase inhibitors. The conclusion is that besides kidney-centered mechanisms, vasoconstrictor mechanisms are also relevant for both the understanding and treatment of this blood pressure phenotype.
Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy
Authors: Tina Sket, Chiara Falcomatà, Dieter Saur
Journal: Cancer Research (2023)

The advent of next-generation sequencing (NGS) and single-cell profiling technologies has revealed the complex and heterogenous ecosystem of human tumors under steady-state and therapeutic perturbation. Breakthroughs in the development of genetically engineered mouse models (GEMM) of human cancers that are based on the combination of two site-specific recombinase systems [dual-recombinase system (DRS)] offer fundamental new possibilities to elucidate and understand critical drivers of the diverse tumor phenotypes and validate potential targets for therapy. Here, we discuss opportunities DRS-based cancer GEMMs offer to model, trace, manipulate, and functionally investigate established cancers, their interactions with the host, and their response to therapy.
Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An <scp>EAACI</scp> position paper
Authors: Jasper Kappen, Zuzana Diamant, Ioana Agache, Matteo Bonini, Jean Bousquet, G. Walter Canonica, Stephen R. Durham, George V. Guibas, Eckard Hamelmann, Marek Jutel, Nikolaos G. Papadopoulos, Graham Roberts, Mohamed H. Shamji, Petra Zieglmayer, Roy Gerth van Wijk, Oliver Pfaar
Journal: Allergy (2023)

In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma.The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers.Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP.This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2023)

Highlights| July 14 2023 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2023 American Association for Cancer Research2023American Association for Cancer Research Clin Cancer Res (2023) 29 (14): 2559. https://doi.org/10.1158/1078-0432.CCR-29-14-HI Related Content A commentary has been published: Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance) A commentary has been published: TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer A commentary has been published: Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes View more A commentary has been published: Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution View less Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record July 14 2023 Citation Selected Articles from This Issue. Clin Cancer Res 15 July 2023; 29 (14): 2559. https://doi.org/10.1158/1078-0432.CCR-29-14-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search It is unclear how plasma 25-hydroxyvitamin D (25[OH]D) is associated with stage III colon cancer outcomes and if such association is mediated by circulating inflammatory cytokines. Using data from a phase III randomized clinical trial, Wang and colleagues found higher 25(OH)D levels were associated with decreased cancer recurrence and improved survival in a possible U-shaped pattern. The protective effect of 25(OH)D was independent of circulating CRP and IL-6 but was marginally mediated by sTNF-R2. Plasma 25(OH)D could be a good prognostic predictor for survival of stage III colon cancer and more studies are suggested to determine whether vitamin D supplementation improves outcomes. The immune checkpoint receptor (ICR) TIGIT has recently been suggested to be involved in pancreatic cancer-immune evasion. Heiduk and colleagues studied single- and co-expression of TIGIT and PD-1 by intratumoral T cells in pancreatic ductal adenocarcinoma (PDAC) and identified distinct T-cell subpopulations. PD-1+TIGIT-conventional CD4+ T... You do not currently have access to this content.
US Health Behaviors in the 21st Century Are Improving, but for Whom?
Authors: John W. Davis
Journal: JAMA Network Open (2023)

Yue Li, MBBS; Peng-Fei Xia, MBBS; Ting-Ting Geng, PhD; Zhou-Zheng Tu, MBBS; Yan-Bo Zhang, PhD; Han-Cheng Yu, MBBS; Ji-Juan Zhang, MBBS; Kunquan Guo, MD; Kun Yang, MD; Gang Liu, PhD; Zhilei Shan, MD, PhD; An Pan, PhD
Evaluation of Unintended Consequences of COVID-19 Pandemic Restrictions and Obesity Prevalence Among Youths
Authors: Stella T. Lartey, Wasantha P. Jayawardene, Stephanie L. Dickinson, Xiwei Chen, Nana Gletsu-Miller, David K. Lohrmann
Journal: JAMA Network Open (2023)

This cohort study examines the association between COVID-19 pandemic restrictions and obesity prevalence among youths aged 2 to 19 years in Monroe County, Indiana.
pH/NIR-responsive and self-healing coatings with bacteria killing, osteogenesis, and angiogenesis performances on magnesium alloy
Authors: Yanbin Zhao, Peng He, Junyan Yao, Mei Li, Bin Wang, Linyuan Han, Zhihai Huang, Chao Guo, Jing Bai, Feng Xue, Yu Cong, Weihua Cai, Paul K. Chu, Chenglin Chu
Journal: Biomaterials (2023)
2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer’s resilience
Authors: Amit Kumar, Saravanan S. Karuppagounder, Yingxin Chen, Carlo Corona, Riki Kawaguchi, Yuyan Cheng, Mustafa Balkaya, Botir T. Sagdullaev, Zhexing Wen, Charles Stuart, Sunghee Cho, Guo-li Ming, Jürgen Tuvikene, Tõnis Timmusk, Daniel H. Geschwind, Rajiv R. Ratan
Journal: Neuron (2023)
“A Community-Engaged Approach to Address Collateral Findings in Embedded Research”
Authors: Emma Tumilty, Elise Smith
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Blurred Boundaries: Toward an Expanded Ethics of Research and Clinical CareResponse to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by the National Center for Advancing Translational Sciences.
Medicine’s Commitment to Science and the Duties That Bind Clinicians
Authors: Rosamond Rhodes, Daniel A. Moros
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Do Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Pragmatic Research and Quality Assessment/Improvement Initiatives: Kindred Spirits
Authors: Ilene Wilets, Glenn Martin, Theodore Bania
Journal: The American Journal of Bioethics (2023)

"Pragmatic Research and Quality Assessment/Improvement Initiatives: Kindred Spirits." The American Journal of Bioethics, 23(8), pp. 69–70This article is referred to by:Blurred Boundaries: Toward an Expanded Ethics of Research and Clinical CareResponse to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
More-Than-Partial Entrustment in Pragmatic Clinical Trials
Authors: Henry S. Richardson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Blurred Boundaries: Toward an Expanded Ethics of Research and Clinical CareThis article refers to:Think Pragmatically: Investigators' Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThe author reported there is no funding associated with the new work featured in this article.
A Neuroethical Analysis of Pragmatic Clinical Trials: Balancing Diverse Interests associated with Collateral Findings
Authors: Michael O. S. Afolabi, Ikeolu O. Afolabi
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Response to Open Peer Commentaries on "Think Pragmatically: Investigators' Obligations to Patient-Subjects When Research is Embedded into Care"This article refers to:Think Pragmatically: Investigators' Obligations to Patient-Subjects When Research is Embedded in Care Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Why Clinicians Do Not Have a Duty to Participate in Pragmatic Clinical Trials
Authors: Bryan Pilkington
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Do Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Treatment over Objection (in Anorexia Nervosa): Capacity Is Not the Whole Story
Authors: Barrie J. Huberman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:"I Don't Want to Gain Weight!" The Ethics of Tube Feeding Over the Objection of a Patient with Anorexia Nervosa Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
End-to-End Integration of Pragmatic Trials Into Health Care Settings
Authors: Sarah M. Greene
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Refusal of Dialysis: Context Matters
Authors: Nekee Pandya, Debjani Mukherjee
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Dialysis Refusal: Discerning the Credibility of a Prior Verbal Directive Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Dialysis Refusal: Discerning the Credibility of a Prior Verbal Directive
Authors: Anita Tarzian
Journal: The American Journal of Bioethics (2023)

"Dialysis Refusal: Discerning the Credibility of a Prior Verbal Directive." The American Journal of Bioethics, 23(8), pp. 88–89This article is referred to by:Not Wanting Dialysis Does Not Necessarily Mean Non-Acceptance—Words MatterRefusal of Dialysis: Context MattersShould the Incapacitated Patient’s Prior Refusal of Dialysis Be Honored? The Value of a Systematic Approach to Gathering Data in an Ethics Consultation Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Distinguishing Clinical and Research Risks in Pragmatic Clinical Trials: The Need for Further Stakeholder Engagement
Authors: Benjamin S. Wilfond, Sinem Toraman Turk, Stephanie A. Kraft, Elliott M. Weiss, Philip I. Tarr, David Schnadower, Stephen B. Freedman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Response to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThis manuscript was supported by R01 AI165327 (BSW, STT, PT, DS, SBF) UL1 TR000423 (BSW, SAK, EMW) and U24 AT009676 (BSW).
Is There a Doctor in the House?
Authors: Donna Chen, Lois Shepherd
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Response to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThis work has been supported in part by NIH/National Center for Advancing Translational Sciences under Award Number NIH/NCATS-UL1TR003015. This content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or the University of Virginia.
Progressing from “Whether to” to “How to” Conduct Pragmatic Trials
Authors: Jonathan D. Casey, Todd W. Rice, Matthew W. Semler
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Response to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingDr. Casey is funded by the National Institute of Health (K23HL153584-01).
Seizing the Opportunity to Improve Ethical Oversight of Clinical Research
Authors: Kirstin Borgerson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Blurred Boundaries: Toward an Expanded Ethics of Research and Clinical CareResponse to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care ACKNOWLEDGEMENTSThe author wishes to thank colleagues in the Department of Bioethics at Dalhousie University for helpful feedback on this commentary.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.